Heat shock proteins (HSPs), a group of highly conserved proteins induced in response to a variety of cellular stresses, appear to be critical for maintaining cellular homeostasis. In this project we are examining the expression of HSPs in rodents in response to physiological stresses in vivo. Our previous studies had demonstrated that simply restraining a rat would elicit the induction of HSP70, the major HSP, in the adrenal gland. More recently, we showed that major vascular structures also elicit this response. Expression of HSP70 in response to restraint is markedly reduced in aged animals. We are currently focusing on the mechanism whereby HSPs are selectively induced in the adrenal and vascular tissues with the hope of understanding why the response declines with age. We have shown that adrenal HSP70 expression with restraint is confined to the cortex of the gland and is dependent on adrenocorticotropic hormone (ACTH). Vascular HSP70 expression occurs in the smooth muscle tissue and is dependent on adrenergic stimulation. Thus, the adrenal and vascular HSP70 expression are differentially regulated. However, both appear to be linked to the classical neuroendocrine stress response which is manifested by the activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system.